[unreadable] The overall aim of the R21 proposal is to investigate the efficacy of a novel acousto-optical elastography method for the early detection and study of skin cancers. The goal of elastographic methods is to image the mechanical behavior of tissues for diagnostic purposes. It is well appreciated that the local mechanical behavior of cancerous tissues differs from that of healthy tissue. It is for this reason that cancerous lesions and tumors are palpable. In the proposed acousto-optical elastography (AOE) method, a low frequency sinusoidally modulated acoustic wave is coupled into the surface of the tissue and serves as a dynamic acoustic force. The tissue displacements and strains resulting from this dynamic loading are tracked and quantified by observing the shifts in a back-projected laser speckle pattern arising from low power laser light scattering from the surface of the tissue. From quantitative knowledge of both the acoustic force and the resulting tissue displacements and strains, both incremental elastic and viscoelastic mechanical behavior of the tissue can be determined. The specific hypothesis of the proposed research is that AOE can discriminate between healthy skin regions and mechanically disparate skin regions, such as areas containing cancerous or pre-cancerous lesions. Successful testing of this hypothesis will provide data on the optimization and characterization of this imaging modality which will lead to preclinical and clinical evaluation of AOE for skin cancer screening and diagnosis. The objectives of the proposal are to: 1) characterize the AOE system on tissue phantoms and on ex-vivo porcine skin in terms of displacement and strain resolution, acoustic frequency and magnitude , and decay and shape of the surface waves as they propagate away from the acoustic source, 2) use AOE to produce 2-D images of both healthy porcine skin and porcine skin with localized lesions present. The influence of lesion size, depth and mechanical contrast between the lesions and the surrounding skin on the ability to detect the lesions will be investigated, and 3) initiate a pilot clinical trial to aid in understanding the physics of this modality on human subjects. Successful completion of these objectives will provide sufficient data to assess the feasibility of AOE for skin cancer imaging and screening and will lead to future preclinical and clinical evaluation of AOE. [unreadable] [unreadable]